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Structural Determination of Apolipoprotein A-I/preb-HDL Particles

EMSL Project ID


Apolipoprotein A-I (apoAI) is a 243-residue exchangeable apolipoprotein that plays a key role in the high-density lipoprotein (HDL) pathway, which clears the "bad cholesterol" from human blood stream. ApoAI is the most abundant protein component in HDL (~70%). Depending on the extent of lipidation, apoAI displays a dramatic conformational plasticity and may adopt one of four distinct conformations: (1). Lipid-free apoAI, (2). ApoAI/prebHDL, (3). ApoAI/DIscHDL, (4). ApoAI/sphericalHDL. Importantly, each conformation mediates one specific biological function, which regulates HDL formation, maturation and transportation. We plan to solve one of the apoAI conformation: apoAI on the prebHDL. Previously, using our 500 MHz and PNNL's high-field NMR instruments, we collected high quality 3D-NMR data set, allowing us to achieve ~85% backbone assignment of this 243-residue protein (MW of prebetaHDL: 55 kDa). We will also collect two 4D-NMR spectral in August. In this proposal, we request more high-field NMR data so that we can finish two other 4D-NMR experiments. These are a set of 4D NMR experiments used for spectral assignment with significant spectral overlap. We anticipate that these 4D-NMR experiments will allow us to completely assign the backbone atoms. We also request 600 MHz NMR time (with a cold probe) for a 3D 15N/13C-filtered NOESY for measurement of apoAI/POPC interaction. These NMR experiments will allow us to solve the structure of apoAI/prebHDL particles.

Project Details

Project type
Capability Research
Start Date
End Date


Principal Investigator

Jianjun Wang
Wayne State University

Team Members

Xuefeng Ren
Wayne State University

Arun Sivashanmugam
Wayne State University

Bin Chen
Wayne State University

Related Publications

A complete backbone spectral assignment of human apolipoprotein AI on a 38 kDa preβHDL (Lp1-AI) particle Xuefeng Ren, Yunhuang Yang, Tracey Neville, David Hoyt, Daniel Sparks, Jianjun Wang
Apolipoprotein AI tertiary structures determine stability and phospholipidbinding activity of discoidal high-density lipoprotein particles of different sizes Bin Chen, Xuefeng Ren, Tracey Neville, Gray Jerome, David W. Hoyt, Daniel Sparks, Gang Ren, and Jianjun Wang Received 14 November 2008; Revised 25 February 2009; Accepted 26 February 2009 DOI: 10.1002/pro.101 Published online 16 March 2009
Chen B, X Ren, T Neville, WG Jerome, DW Hoyt, DL Sparks, G Ren, and J Wang. 2009. "Apolipoprotein AI tertiary structures determine stability and phospholipid-binding activity of discoidal high-density lipoprotein particles of different sizes." Protein Science 18(5):921-935. doi:10.1002/pro.101